US2009239241A1PendingUtilityA1

Methods and compositions for diagnosis, stratification, and monitoring of alzheimer's disease and other neurological disorders in body fluids

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Assignee: RAY SANDIPPriority: Nov 19, 2003Filed: Jun 8, 2009Published: Sep 24, 2009
Est. expiryNov 19, 2023(expired)· nominal 20-yr term from priority
Inventors:Sandip RayAnton Wyss-Coray
G01N 2800/2821G01N 2800/28G01N 33/6896C12Q 1/6883G01N 2800/60
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Claims

Abstract

The inventors have discovered a collection of proteinaceous biomarkers (“AD biomarkers) which can be measured in peripheral biological fluid samples to aid in the diagnosis of neurodegenerative disorders, particularly Alzheimer's disease and mild cognitive impairment (MCI). The invention further provides methods of identifying candidate agents for the treatment of Alzheimer's disease by testing prospective agents for activity in modulating AD biomarker levels.

Claims

exact text as granted — not AI-modified
1 . A method of aiding diagnosis of Alzheimer's disease (“AD”), comprising comparing a measured level of at least one AD diagnosis biomarker in a biological fluid sample from an individual to a reference level for the biomarker, wherein the AD diagnosis biomarker is selected from the group consisting of GCSF; IFN-g; IGFBP-1; BMP-6; BMP-4; Eotaxin-2; IGFBP-2; TARC; RANTES; ANG; PARC; Acrp30; AgRP(ART); TIMP-1; TIMP-2; ICAM-1; TRAIL R3; uPAR; IGFBP-4; LEPTIN(OB); PDGF-BB; EGF; BDNF; NT-3; NAP-2; IL-1ra; MSP-a; SCF; TGF-b3; TNF-b; MIP-1d; IL-3; FGF-6; IL-6 R; sTNF RII; AXL; bFGF; FGF-4; CNTF; MCP-1; MIP-1b; TPO; VEGF-B; IL-8; FAS; EGF-R. 
   
   
       2 . The method of  claim 1 , comprising comparing the measuring level of at least two AD diagnosis biomarkers to a reference level for the biomarkers. 
   
   
       3 . The method of  claim 1 , comprising comparing the measured level of at least three AD diagnosis biomarkers to a reference level for the biomarkers. 
   
   
       4 . The method of  claim 1 , comprising comparing the measured level of at least four AD diagnosis biomarkers to a reference level for the biomarkers. 
   
   
       5 . The method of  claim 1 , comprising comparing the measured level of at least five AD diagnosis biomarkers to a reference level for the biomarkers. 
   
   
       6 . The method of  claim 1 , wherein comparing the measured value to a reference value for each AD diagnosis biomarker measured comprises calculating the fold difference between the measured value and the reference value. 
   
   
       7 . A method of aiding diagnosis of Alzheimer's disease (“AD”), comprising:
 comparing a measured level of at least one AD diagnosis biomarker in a biological sample fluid sample from an individual to a reference level for the biomarker wherein the AD diagnosis biomarker is selected from the group consisting BTC; SDF-1; MCP-2; IFN-gamma; IGFBP-4; IGF-1SR; IL-8; GM-CSF; and ANG-2.   
   
   
       8 . The method of  claim 7 , comprising comparing the measuring level of at least two AD diagnosis biomarkers to a reference level for the biomarkers. 
   
   
       9 . The method of  claim 7 , comprising comparing the measured level of at least three AD diagnosis biomarkers to a reference level for the biomarkers. 
   
   
       10 . The method of  claim 7 , comprising comparing the measured level of at least four AD diagnosis biomarkers to a reference level for the biomarkers. 
   
   
       11 . The method of  claim 7 , comprising comparing the measured level of at least five AD diagnosis biomarkers to a reference level for the biomarkers. 
   
   
       12 . The method of  claim 7  wherein the at least one AD diagnosis biomarker is selected from the group consisting of biomarkers IFN-gamma and IL-8. 
   
   
       13 . A method of aiding diagnosis of Alzheimer's disease (“AD”), comprising:
 comparing a measured level of at least one AD diagnosis biomarker in a biological sample fluid sample from an individual to a reference level for the biomarker wherein the AD diagnosis biomarker is selected from the group consisting of TNF RII; MSP-alpha; uPAR; TPO; MIP-1beta; VEGF-beta; FAS; MCP-1; NAP-2; ICAM-1; TRAIL R3; PARC; ANG; IL-3; MIP-1delta; IFN-gamma; IL-8; and FGF-6.   
   
   
       14 . The method of  claim 13 , comprising comparing the measuring level of at least two AD diagnosis biomarkers to a reference level for the biomarkers. 
   
   
       15 . The method of  claim 13 , comprising comparing the measured level of at least three AD diagnosis biomarkers to a reference level for the biomarkers. 
   
   
       16 . The method of  claim 13 , comprising comparing the measured level of at least four AD diagnosis biomarkers to a reference level for the biomarkers. 
   
   
       17 . The method of  claim 13 , comprising comparing the measured level of at least five AD diagnosis biomarkers to a reference level for the biomarkers. 
   
   
       18 . A method of aiding diagnosis of Alzheimer's disease (“AD”), comprising:
 comparing a measured level of at least one AD diagnosis biomarker in a biological sample fluid sample from an individual to a reference level for the biomarker wherein the AD diagnosis biomarker is selected from the group consisting of lymphotactin and IL-11.   
   
   
       19 . The method of  claim 7  or  claim 13 , wherein said biological fluid sample is a peripheral biological fluid sample. 
   
   
       20 . A method for monitoring progression of Alzheimer's disease (AD) in an AD patient, comprising comparing a measured level of at least one AD diagnosis biomarker in a biological sample fluid sample from an individual to a reference level for the biomarker wherein the AD diagnosis biomarker is selected from the group consisting of lymphotactin and IL-11. 
   
   
       21 . The method of  claim 20 , wherein said reference level is a level obtained from a biological fluid sample from the same AD patient at an earlier point in time. 
   
   
       22 . The method of  claim 20  wherein the biological fluid sample is a peripheral biological fluid sample. 
   
   
       23 . A method for stratifying Alzheimer's disease (AD) in an individual, comprising:
 comparing a measured level of at least one AD diagnosis biomarker in a biological sample from the individual with a reference level for the at least one biomarker, wherein the at least one biomarker is selected from the group consisting of lymphotactin and IL-11.   
   
   
       24 . The method of  claim 23  wherein said biological fluid sample is a peripheral fluid sample. 
   
   
       25 . A kit for use in aiding in the diagnosis of AD, wherein the kit comprises at least one reagent specific for at least one AD diagnosis marker, wherein said at least one AD diagnosis biomarker is selected from the group consisting of BTC; SDF-1; MCP-2; IFN-gamma; IGFBP-4; IGF-1 SR; IL-8; GM-CSF; and ANG-2, and instructions for carrying out a method of aiding in the diagnosis of AD. 
   
   
       26 . The kit of  claim 25  wherein the at least one AD diagnosis biomarker is selected from the group consisting of biomarkers IFN-gamma and IL-8. 
   
   
       27 . A kit for use in aiding in the diagnosis of AD, wherein the kit comprises at least one reagent specific for at least one AD diagnosis marker, wherein said at least one AD diagnosis biomarker is selected from the group consisting of sTNF RII; MSP-alpha; uPAR; TPO; MIP-1 beta; VEGF-beta; FAS; MCP-1; NAP-2; ICAM-1; TRAIL R3; PARC; ANG; IL-3; MIP-1delta; IFN-gamma; IL-8; and FGF-6, and instructions for carrying out a method of aiding in the diagnosis of AD. 
   
   
       28 . A kit for use in aiding in the diagnosis of AD, wherein the kit comprises at least one reagent specific for at least one AD diagnosis marker, wherein said at least one AD diagnosis biomarker is selected from the group consisting of the biomarkers lymphotactin and IL-11, and instructions for carrying out a method of aiding in the diagnosis of AD. 
   
   
       29 . The kit of  claim 28  wherein the reagent specific for the AD diagnosis biomarker is an antibody, or fragment thereof, that is specific for the AD diagnosis biomarker. 
   
   
       30 . The kit of  claim 28  further comprising at least one biomarker for normalizing data. 
   
   
       31 . The kit of  claim 30  wherein said biomarker for normalizing data is selected from the group consisting of TGF-beta and TGF-beta3. 
   
   
       32 . A method for identifying at least one biomarker useful for the diagnosis of a neurological disease, comprising:
 obtaining measured values from a set of peripheral biological fluid samples for a plurality of biomarkers, wherein said set of peripheral biological fluid samples is divisible into subsets on the basis of a neurological disease; comparing the measured values from each subset for at least one biomarker; and identifying at least one biomarker for which the measured values are significantly different between the subsets.   
   
   
       33 . The method of  claim 32  wherein the neurological disease is AD. 
   
   
       34 . A method of aiding diagnosis of a neurodegenerative disease comprising obtaining measured values of one or more biomarkers shown in Table 12A-12B with a q-value % of less than 1.5, and comparing the measured value to a reference value.

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